Variant rs2717477 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001378609.3(OTOGL):c.7047G>A(p.Thr2349=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 1,577,228 control chromosomes in the GnomAD database, including 521,972 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T2349T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.72 ( 40882 hom., cov: 31)

Exomes 𝑓: 0.82 ( 481090 hom. )

Consequence

OTOGL
NM_001378609.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.90

Variant links:

Genes affected

OTOGL (HGNC:26901): (otogelin like) The protein encoded by this gene belongs to the otogelin family. This gene is expressed in the inner ear of vertebrates with the highest level of expression seen at the embryonic stage and lowest in adult. Knockdown studies in zebrafish suggest that this gene is essential for normal inner ear function. Mutations in this gene are associated with autosomal recessive deafness. [provided by RefSeq, Dec 2012]

OTOGL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 12-80378033-G-A is Benign according to our data. Variant chr12-80378033-G-A is described in ClinVar as [Benign]. Clinvar id is 226976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-80378033-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.9 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTOGL	NM_001378609.3 linkuse as main transcript	c.7047G>A	p.Thr2349=	synonymous_variant	59/59	ENST00000547103.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTOGL	ENST00000547103.7 linkuse as main transcript	c.7047G>A	p.Thr2349=	synonymous_variant	59/59	5	NM_001378609.3	P1

Frequencies

GnomAD3 genomes

AF:

0.717

AC:

108874

AN:

151760

Hom.:

40880

Cov.:

show subpopulations

Gnomad AFR

AF:

0.469

Gnomad AMI

AF:

0.774

Gnomad AMR

AF:

0.703

Gnomad ASJ

AF:

0.840

Gnomad EAS

AF:

0.783

Gnomad SAS

AF:

0.819

Gnomad FIN

AF:

0.792

Gnomad MID

AF:

0.782

Gnomad NFE

AF:

0.839

Gnomad OTH

AF:

0.758

GnomAD3 exomes

AF:

0.769

AC:

152312

AN:

198162

Hom.:

59710

AF XY:

0.783

AC XY:

82601

AN XY:

105560

show subpopulations

Gnomad AFR exome

AF:

0.458

Gnomad AMR exome

AF:

0.619

Gnomad ASJ exome

AF:

0.838

Gnomad EAS exome

AF:

0.765

Gnomad SAS exome

AF:

0.827

Gnomad FIN exome

AF:

0.793

Gnomad NFE exome

AF:

0.838

Gnomad OTH exome

AF:

0.788

GnomAD4 exome

AF:

0.818

AC:

1166610

AN:

1425350

Hom.:

481090

Cov.:

AF XY:

0.820

AC XY:

579030

AN XY:

705764

show subpopulations

Gnomad4 AFR exome

AF:

0.449

Gnomad4 AMR exome

AF:

0.632

Gnomad4 ASJ exome

AF:

0.835

Gnomad4 EAS exome

AF:

0.772

Gnomad4 SAS exome

AF:

0.826

Gnomad4 FIN exome

AF:

0.799

Gnomad4 NFE exome

AF:

0.839

Gnomad4 OTH exome

AF:

0.802

GnomAD4 genome

AF:

0.717

AC:

108904

AN:

151878

Hom.:

40882

Cov.:

AF XY:

0.718

AC XY:

53281

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.468

Gnomad4 AMR

AF:

0.703

Gnomad4 ASJ

AF:

0.840

Gnomad4 EAS

AF:

0.782

Gnomad4 SAS

AF:

0.819

Gnomad4 FIN

AF:

0.792

Gnomad4 NFE

AF:

0.839

Gnomad4 OTH

AF:

0.758

Alfa

AF:

0.819

Hom.:

117254

Bravo

AF:

0.695

Asia WGS

AF:

0.782

AC:

2720

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Thr2340Thr in exon 58 of OTOGL: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 49.5% (2182/4404) of African American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2717477). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.013

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over